Mitochondrial proton and electron leaks
Open accessAbstract
Mitochondrial proton and electron leak have a major impact on mitochondrial coupling efficiency and production of reactive oxygen species. In the first part of this chapter, we address the molecular nature of the basal and inducible proton leak pathways, and their physiological importance. The basal leak is unregulated, and a major proportion can be attributed to mitochondrial anion carriers, whereas the proton leak through the lipid bilayer appears to be minor. The basal proton leak is cell-type specific and correlates with metabolic rate. The inducible leak through the ANT (adenine nucleotide translocase) and UCPs (uncoupling proteins) can be activated by fatty acids, superoxide or lipid peroxidation products. The physiological role of inducible leak through UCP1 in mammalian brown adipose tissue is heat production, whereas the roles of non-mammalian UCP1 and its paralogous proteins, in particular UCP2 and UCP3, are not yet resolved. The second part of the chapter focuses on the electron leak that occurs in the mitochondrial electron transport chain. Exit of electrons prior to the reduction of oxygen to water at cytochrome c oxidase causes superoxide production. As the mechanisms of electron leak are crucial to understanding their physiological relevance, we summarize the mechanisms and topology of electron leak from complexes I and III in studies using isolated mitochondria. We also highlight recent progress and challenges of assessing electron leak in the living cell. Finally, we emphasize the importance of proton and electron leak as therapeutic targets in body mass regulation and insulin secretion.
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Basal proton leak depends on inner mitochondrial membrane composition and can account for up to 30-50% of resting cellular metabolic rate.
“This process essentially depends on the composition of the inner mitochondrial membrane and could account for up to 30–50% of the resting cellular metabolic rate [3].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [3]
This coupling is not complete and leads to the production of ROS, a process called electron leak.
“However, this coupling is not complete and leads in fine to the production of ROS, a process called electron leak [3] (Figure 2).”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [3]
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“Electron slip consists of the transfer of electrons through the respiratory complexes without proton pumping [3,4].”
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- Authors
- Jastroch, M., Divakaruni, A. S., Mookerjee, S., Treberg, J. R., & Brand, M. D.
- Affiliations
- Buck Institute for Research on Aging (US)
- Venue
- Essays in Biochemistry
- Publisher
- Portland Press Ltd.
- Published
- 2010-06-14
- Volume
- 47
- Pages
- 53-67
- ISSN
- 0071-1365 (ISSN-L)
- 1744-1358
- PMC
- PMC3122475
- OpenAlex
- W2139200038
- Cited by
- 829
- References
- 52
- Citations by year
- 2026: 39 · 2025: 69 · 2024: 68 · 2023: 59 · 2022: 69 · 2021: 73 · 2020: 77 · 2019: 79 · 2018: 67 · 2017: 49 · 2016: 44 · 2015: 49 · 2014: 27 · 2013: 23 · 2012: 23
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Essays in Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- Funders
- National Institute on Aging (R01AG033542, PL1AG032118, P01AG025901, P30AG025708)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial proton leak, mitochondrial coupling efficiency, reactive oxygen species, adenine nucleotide translocase, uncoupling proteins, UCP1, brown adipose tissue thermogenesis, UCP2, UCP3, superoxide production, cytochrome c oxidase, electron transport chain, complex I, cytochrome bc1 complex, fatty acid activation, lipid peroxidation, body weight regulation, insulin secretion
- MeSH terms
- Animals, Electron Transport, Humans, Mitochondria, Models, Biological, Protons, Mitochondrial Proteins
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